Lipoglycans Contribute to Innate Immune Detection of Mycobacteria

Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purifie...

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Main Authors:	Krishna, Shyam, Ray, Aurélie, Dubey, Shiv K., Larrouy-Maumus, Gérald, Chalut, Christian, Castanier, Romain, Noguera, Audrey, Gilleron, Martine, Puzo, Germain, Vercellone, Alain, Nampoothiri, K. Madhavan, Nigou, Jérôme
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229593/

id	pubmed-3229593
recordtype	oai_dc
spelling	pubmed-32295932011-12-07 Lipoglycans Contribute to Innate Immune Detection of Mycobacteria Krishna, Shyam Ray, Aurélie Dubey, Shiv K. Larrouy-Maumus, Gérald Chalut, Christian Castanier, Romain Noguera, Audrey Gilleron, Martine Puzo, Germain Vercellone, Alain Nampoothiri, K. Madhavan Nigou, Jérôme Research Article Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs. Public Library of Science 2011-12-02 /pmc/articles/PMC3229593/ /pubmed/22164297 http://dx.doi.org/10.1371/journal.pone.0028476 Text en Krishna et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Krishna, Shyam Ray, Aurélie Dubey, Shiv K. Larrouy-Maumus, Gérald Chalut, Christian Castanier, Romain Noguera, Audrey Gilleron, Martine Puzo, Germain Vercellone, Alain Nampoothiri, K. Madhavan Nigou, Jérôme
spellingShingle	Krishna, Shyam Ray, Aurélie Dubey, Shiv K. Larrouy-Maumus, Gérald Chalut, Christian Castanier, Romain Noguera, Audrey Gilleron, Martine Puzo, Germain Vercellone, Alain Nampoothiri, K. Madhavan Nigou, Jérôme Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
author_facet	Krishna, Shyam Ray, Aurélie Dubey, Shiv K. Larrouy-Maumus, Gérald Chalut, Christian Castanier, Romain Noguera, Audrey Gilleron, Martine Puzo, Germain Vercellone, Alain Nampoothiri, K. Madhavan Nigou, Jérôme
author_sort	Krishna, Shyam
title	Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
title_short	Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
title_full	Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
title_fullStr	Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
title_full_unstemmed	Lipoglycans Contribute to Innate Immune Detection of Mycobacteria
title_sort	lipoglycans contribute to innate immune detection of mycobacteria
description	Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (∼1.7 fold) or reduced (∼2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-κB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229593/
_version_	1611491565917700096

Lipoglycans Contribute to Innate Immune Detection of Mycobacteria

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